This project focuses on the known phenomenon of oscillations of [Ca2+]i in rat megakaryocytes. These oscillations are known to be inhibited reversibly upon increase of intracellular levels of cGMP or cAMP. Further, electrophysiological evidence suggests that the mechanism of activation of Ca oscillations in megakaryocytes and platelets is different from that in many other cell types in that these cells do not express ryanodine- or caffeine-sensitive Ca stores. The proposal is to use the imaging capabilities of the National Resource to further the experimental dissection of the calcium oscillations and to use the Virtual Cell to model this process, which appears to function with less complexity than other calcium oscillators. The PI suggests that the geometry, simple pharmacology and single Ca2+ release system of megakaryocytes makes them good candidates for study by the Virtual Cell. The Study Section concurs in this view. This project fits well with the proposed use of the National Re source, and, as its focus is an calcium dynamics, also will benefit from the core project on Ca dynamics. The Study Section is positive toward this project.